Theodore C. Pierson, PhD

Chief, Viral Pathogenesis Section

Chief, Laboratory of Viral Disease

The research interests of my laboratory center around flaviviruses, a class of vector-borne RNA viruses that can cause a range of potentially severe diseases in humans, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, congenital abnormalities, and fetal death. Flaviviruses have become globally distributed and are responsible for infecting up to 400 million people annually. Moreover, outbreaks of less well-characterized flaviviruses in humans and animals in various regions of the world have caused significant concern.

Neutralizing antibodies (Nabs), which bind to the virus's surface and directly inhibit its infectivity, are a critical correlate of vaccine-elicited protection for many flaviviruses. However, understanding humoral immunity to flaviviruses is complicated by the potential for virus-reactive antibodies to augment the infection of Fc-receptor-expressing cells. This mechanism, known as antibody-dependent enhancement of infection (ADE), has been mechanistically linked to severe dengue fever disease. Developing a dengue fever vaccine that can elicit protection against four groups of antigenically-related viruses that share only some of the epitopes that contribute to protection while avoiding sensitizing the recipient to severe infection outcomes is a critical challenge.

Our primary goal is to understand the mechanisms of action of anti-flavivirus antibodies, the complexity of antibody responses elicited by flavivirus infection or vaccination, and the antigenic features of protective vaccine antigens. To achieve this goal, my team uses various experimental approaches, including in vitro and in vivo models, to investigate the mechanisms of antibody-mediated protection and viral pathogenesis, identify correlates of protection, and develop new strategies for vaccine design and evaluation.